Abstract
OBJECTIVE: The authors' objective was to quantitatively assess angiogenesis or neovascularity within node-negative colon cancers and to determine if increased angiogenesis correlated with higher recurrence and lower survival rates. SUMMARY BACKGROUND DATA: Neovascularization promotes rapid tumor growth by facilitating nutrient and metabolite exchange. Recent work with breast and nonsmall cell lung cancers has shown that low angiogenic activity imparts a lower risk of recurrence and metastasis. Although adjuvant therapy is beneficial for patients with node-positive colon cancers, no such benefit has been demonstrated for patients with node-negative lesions. Nevertheless, up to 30% of this latter group will experience recurrence. We sought to identify a subset of patients with node-negative colon cancers at high risk for recurrence who might benefit from such therapy. METHODS: One hundred five node-negative colon cancers were immunostained for endothelial cell factor VIII-related antigen. Blood vessels within three microscopic fields at 100X magnification were counted, the mean calculated, and an angiogenesis score assigned. A subjective angiogenesis grade (1-4) was assigned after each slide was surveyed in its entirety. Score and grade were then assessed with respect to cancer recurrence and patient survival. RESULTS: Mean patient age was 71 years (range, 41-90 years) and mean tumor size, 5.6 cm (range, 2-12 cm). Mean follow-up was 6.5 years; mean angiogenesis score, 27.9 (range, 4-50); and mean grade, 2.0 (range, 1-4). Patients living 5 years had significantly lower angiogenesis scores than did nonsurvivors (22.8 vs. 43.2, p = 0.0004). Each 10-vessel increase in score imparted a 2.0-fold greater hazard of death and a 2.7-fold greater hazard of recurrence. The probability of surviving 5 years is estimated by: [formula: see text] and the probability of recurrence is estimated by: [formula: see text] CONCLUSIONS: Angiogenesis within colon cancer is an important predictor of tumor behavior and may identify patients at higher risk for recurrence and early death.
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- FOLKMAN J., LONG D. M., Jr, BECKER F. F. Growth and metastasis of tumor in organ culture. Cancer. 1963 Apr;16:453–467. doi: 10.1002/1097-0142(196304)16:4<453::aid-cncr2820160407>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
- Folkman J., Cotran R. Relation of vascular proliferation to tumor growth. Int Rev Exp Pathol. 1976;16:207–248. [PubMed] [Google Scholar]
- Folkman J. The role of angiogenesis in tumor growth. Semin Cancer Biol. 1992 Apr;3(2):65–71. [PubMed] [Google Scholar]
- Galandiuk S., Wieand H. S., Moertel C. G., Cha S. S., Fitzgibbons R. J., Jr, Pemberton J. H., Wolff B. G. Patterns of recurrence after curative resection of carcinoma of the colon and rectum. Surg Gynecol Obstet. 1992 Jan;174(1):27–32. [PubMed] [Google Scholar]
- Horak E. R., Leek R., Klenk N., LeJeune S., Smith K., Stuart N., Greenall M., Stepniewska K., Harris A. L. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet. 1992 Nov 7;340(8828):1120–1124. doi: 10.1016/0140-6736(92)93150-l. [DOI] [PubMed] [Google Scholar]
- Macchiarini P., Fontanini G., Hardin M. J., Squartini F., Angeletti C. A. Relation of neovascularisation to metastasis of non-small-cell lung cancer. Lancet. 1992 Jul 18;340(8812):145–146. doi: 10.1016/0140-6736(92)93217-b. [DOI] [PubMed] [Google Scholar]
- Michelassi F., Vannucci L., Ayala J. J., Chappel R., Goldberg R., Block G. E. Local recurrence after curative resection of colorectal adenocarcinoma. Surgery. 1990 Oct;108(4):787–793. [PubMed] [Google Scholar]
- Moertel C. G., Fleming T. R., Macdonald J. S., Haller D. G., Laurie J. A., Goodman P. J., Ungerleider J. S., Emerson W. A., Tormey D. C., Glick J. H. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990 Feb 8;322(6):352–358. doi: 10.1056/NEJM199002083220602. [DOI] [PubMed] [Google Scholar]
- Pinkus G. S., Etheridge C. L., O'Connor E. M. Are keratin proteins a better tumor marker than epithelial membrane antigen? A comparative immunohistochemical study of various paraffin-embedded neoplasms using monoclonal and polyclonal antibodies. Am J Clin Pathol. 1986 Mar;85(3):269–277. doi: 10.1093/ajcp/85.3.269. [DOI] [PubMed] [Google Scholar]
- Srivastava A., Laidler P., Davies R. P., Horgan K., Hughes L. E. The prognostic significance of tumor vascularity in intermediate-thickness (0.76-4.0 mm thick) skin melanoma. A quantitative histologic study. Am J Pathol. 1988 Nov;133(2):419–423. [PMC free article] [PubMed] [Google Scholar]
- Stipa S., Nicolanti V., Botti C., Cosimelli M., Mannella E., Stipa F., Giannarelli D., Bangrazi C., Cavaliere R. Local recurrence after curative resection for colorectal cancer: frequency, risk factors and treatment. J Surg Oncol Suppl. 1991;2:155–160. doi: 10.1002/jso.2930480532. [DOI] [PubMed] [Google Scholar]
- Weidner N., Folkman J., Pozza F., Bevilacqua P., Allred E. N., Moore D. H., Meli S., Gasparini G. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 1992 Dec 16;84(24):1875–1887. doi: 10.1093/jnci/84.24.1875. [DOI] [PubMed] [Google Scholar]
- Weidner N., Semple J. P., Welch W. R., Folkman J. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med. 1991 Jan 3;324(1):1–8. doi: 10.1056/NEJM199101033240101. [DOI] [PubMed] [Google Scholar]